title: Non-24-Hour Disorder in Blind Individuals Revisited: Variability and the Influence of Environmental Time Cues.
abstract: OBJECTIVE
  To assess the interindividual and intraindividual variability in the circadian rhythms of blind individuals with non-24-h disorder and to quantify the influence of environmental time cues in blind subjects lacking entrainment (non-24-h individuals or N-24s).
  
  
  METHODS
  An observational study of 21 N-24s (11 females and 10 males, age 9-78 years) who kept a sleep/wake schedule of their choosing. Circadian phase was determined using the melatonin onset (MO) from plasma or saliva samples that were collected every 2 weeks. Melatonin concentrations were measured by radioimmunoassay. A total of 469 MO assessments were conducted over 5,536 days of study. The rate of drift of circadian phase was calculated using a series of MOs (total number of hours the MO drifted divided by the total number of days studied). Stability of the rest/activity rhythm was calculated using chi-squared periodogram analysis of wrist actigraphy data in 19 subjects.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Paid volunteers.
  
  
  METHODS
  N/A.
  
  
  RESULTS
  Subjects lacked entrainment such that circadian phase drifted an average (± standard deviation) of 0.39 ± 0.29 h later per day; however, there was notable intersubject and intrasubject variability in the rate of drift including relative coordination and periods of transient entrainment during which there was little to no drift in the circadian phase. A regular, reproducible, and significant oscillation in the rate of drift was detected in 14 of the 21 subjects. A significant non-24-h rest/activity rhythm was detected in 18 of 19 subjects. There was a strong correlation (r = 0.793, P = 0.0001) between the non-24-h rest/activity rhythm and the rate of drift of the circadian phase.
  
  
  CONCLUSIONS
  Most N-24s are influenced by unidentified environmental time cues and the non-entrained biological clock in such N-24s is reflected in their rest/activity rhythms. These findings may have diagnostic and treatment implications: this disorder might be diagnosed with actigraphy alone, relative coordination and transient entrainment may result in misdiagnosis and responsiveness to environmental time cues may influence treatment success with oral melatonin.
  
  
  BACKGROUND
  Emens JS; Laurie AL; Songer JB; Lewy AJ. Non-24-hour disorder in blind individuals revisited: variability and the influence of environmental time cues.SLEEP2013;36(7):1091-1100.
authors.affiliation: Sleep and Mood Disorders Laboratory, Department of Psychiatry, Oregon Health & Science University, Portland, OR.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Emens
authors.forename: Amber L
authors.initials: AL
authors.lastname: Laurie
authors.forename: Jeannie B
authors.initials: JB
authors.lastname: Songer
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Lewy
keywords: Blind; circadian; melatonin; non-24-h disorder